Radioactive photoactive drug analogues have been used to identify specific drug binding targets in multidrug-resistant cells. A 150-180 kDalt surface membrane glycoprotein (gp150-180) has been identified in drug-resistant but not in drug-sensitive parental cells. Gp150-180 exhibits cross binding specificity for Vinca alkaloids, actinomycin D, anthracycline antibiotics, calcium channel blockers and calmodulin inhibitors suggesting a central functional role in the multidrug-resistant phenotype. The role of gp150-180 in drug-resistance will be tested by examining the effect of specific drug photolabeling on cellular drug uptake and efflux. The subcellular distribution of gp150-180 will be determined. A functional gp150-180 will be purified. Anti-gp150-180 monoclonal antibodies will be prepared and gp150-180 plasma membrane orientation with respect to drug binding sites will be determined. Partial amino acid sequence analysis will be used to construct specific gp150-180 cDNA probes. Purified gp150-180 will be inserted into planar lipid bilayers for functional reconstitution studies. The biochemical role(s) of gp150-180 in drug resistance will be studied in order to design new agents for circumventing the multidrug-resistant phenomenon.